The natural history of benign thyroid nodules.

IMPORTANCE: Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious nodules. Current guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed. OBJECTIVE: To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed. MAIN OUTCOMES AND MEASURES: Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up. RESULTS: Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes ≥1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer. CONCLUSIONS AND RELEVANCE: Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.

Vandetanib: opening a new treatment practice in advanced medullary thyroid carcinoma.

Medullary thyroid cancer (MTC) is frequently diagnosed in a locally advanced or metastatic stage, and 10-year survival rates in these cases are below 20 %. Cytotoxic chemotherapy has no significant impact on overall or progression-free survival. Vandetanib (Caprelsa(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors. It is the first systemic drug with demonstrated anti-tumor benefits in advanced MTC, and it has recently been approved for locally advanced or metastatic MTC by the United States Food and Drug Administration (April 2011) and the European Medicines Agency (February 2012). This review, starting from the phases II and III efficacy and safety data that led to these approvals, explores important issues related to dosing, patient selection, and strategies for managing the substantial risk of toxicity associated with the drug (including life-threatening cardiac events that are the subject of a black-box warning in the United States). All these issues still remain to be defined. Vandetanib is becoming a standard of care for symptomatic, progressive, metastatic MTCs, to be used selectively in those patients who are likely to benefit from it.

Long-term surveillance of papillary thyroid cancer patients who do not undergo postoperative radioiodine remnant ablation: is there a role for serum thyroglobulin measurement?

CONTEXT: Serum thyroglobulin (Tg) assays are considered fundamental in postoperative surveillance of differentiated thyroid cancer (DTC) patients. However, the postsurgical profile of Tg levels has never been specifically investigated in patients who do not undergo radioiodine remnant ablation (RRA). OBJECTIVES: Our objective was to explore the evolution of Tg levels over time in DTC patients treated with total or near-total thyroidectomy without RRA. DESIGN: We retrospectively analyzed 290 consecutively diagnosed cases of low-risk (American Thyroid Association criteria) DTC treated with thyroidectomy alone and followed yearly with neck ultrasonography and serum Tg assays. We compared final Tg values in this group and a matched group of 495 RRA-positive patients. Temporal trends of serial Tg levels were also analyzed in 78 of the RRA-negative patients monitored with a high-sensitivity immunoradiometric assay. RESULTS: After follow-up of 2.5-22 yr (median 5 yr), final Tg levels were undetectable (<1 ng/ml) in 274 of 290 RRA-negative patients (95%) and 492 of 495 RRA-positive controls (99%). In the subset of 78 RRA-negative patients, undetectable Tg levels (<0.2 ng/ml) were recorded in 60% at the first postoperative evaluation (3-12 months) and in 79% after 5 yr. Tg levels increased in the single patient who experienced disease recurrence during the observation period. CONCLUSION: In most RRA-negative patients, postoperative serum Tg values spontaneously drop to undetectable levels within 5-7 yr after thyroidectomy. Thus, in later phases, Tg assays may be a valuable tool for follow-up even in patients who do not undergo RRA.

[Benign thyroid nodules: diagnostic and therapeutic approach]. / Noduli tiroidei benigni: guida ad una razionale scelta diagnostico-terapeutica.

In the last years an increase in thyroid nodules detection has been reported from several epidemiological studies. This trend is largely due to the routine use of diagnostic sonography procedures in clinical practice. Thyroid nodules, both palpable or not palpable, rarely turn out to be malignant. Fine-needle aspiration cytology (FNAc) plays a central role in establishing the nature of the nodule. Excluded the presence of malignant lesions, which are generally treated with surgery, physicians are faced with a variety of therapeutic options, and choosing the optimal approach can be a difficult task. These include a periodic follow-up alone without treatment, the iodine supplementation, the thyroid-hormone suppressive therapy, the radioiodine administration, the percutaneous ethanol injections, and the new technique of laser photocoagulation. In all cases, decisions on the management of benign thyroid nodules should always be based on clinical target and a careful analysis of benefits and risks to the patient.